microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy

Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin P...

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Autores principales: Dong H, Dong B, Zhang N, Liu S, Zhao H
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Publicado: Dove Medical Press 2020
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spelling oai:doaj.org-article:819b05184c634e61bd77dd5dd3b63bfb2021-12-02T09:54:49ZmicroRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy1178-2021https://doaj.org/article/819b05184c634e61bd77dd5dd3b63bfb2020-01-01T00:00:00Zhttps://www.dovepress.com/microrna-182-negatively-influences-the-neuroprotective-effect-of-apeli-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin Province 130021, People’s Republic of China; 3Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Huiying ZhaoDepartment of Geriatric Medicine, The First Hospital of Jilin University, Changchun 130021, People’s Republic of ChinaTel +86-431-88783239Fax +86-431-88786439Email zhaohuiyingjdyy@126.comSongyan LiuDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86-431-84595348Fax +86-431-84596133Email songyanliujilin@163.comPurpose: To explore the neuroprotective effects and mechanisms of Apelin (APLN), and to study the regulation of APLN expression by microRNA (miRNA) in epilepsy.Materials and Methods: In vitro and in vivo epileptic models were established with hippocampal neurons and Wistar rats. Apoptosis of neurons was identified by flow cytometry. Western blotting was used to detect the expression of proteins, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to analyze the expression of miRNA and messenger RNA (mRNA). Bioinformatics software was used to predict target genes of miRNA, which were confirmed by dual-luciferase reporter gene system and functional experiments.Results: Our study demonstrated protective effects of APLN against neuronal death in epilepsy both in vitro and in vivo. The underlying mechanisms involved are inhibiting the expression of metabotropic glutamate receptor 1 (mGluR1), Bax, and caspase-3; promoting the expression of Bcl-2; and increasing phosphorylated-AKT (p-AKT) levels in neurons. For the first time, we found that miR-182 could negatively regulate both transcriptional and translational levels of APLN, and that the up-regulation of miR-182 inhibited the expression of APLN and Bcl-2, and promoted the expression of Bax and caspase-3.Conclusion: APLN could protect the neurons from injury in epilepsy by regulating the expression of apoptosis-associated proteins and mGluR1 and increasing p-AKT levels, which were attenuated by miR-182. Hence, miR-182/APLN may be potential targets for epilepsy control and treatment.Keywords: epilepsy, apelin, neuroprotective effects, miR-182, regulationDong HDong BZhang NLiu SZhao HDove Medical Pressarticleepilepsyapelinneuroprotective effectsmir-182regulationNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 327-338 (2020)
institution DOAJ
collection DOAJ
language EN
topic epilepsy
apelin
neuroprotective effects
mir-182
regulation
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle epilepsy
apelin
neuroprotective effects
mir-182
regulation
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Dong H
Dong B
Zhang N
Liu S
Zhao H
microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
description Han Dong,1 Bin Dong,1 Na Zhang,2 Songyan Liu,3 Huiying Zhao1 1Department of Geriatric Medicine, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of China; 2Department of Electrical Diagnosis, Jilin Province FAW General Hospital, Changchun, Jilin Province 130021, People’s Republic of China; 3Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaCorrespondence: Huiying ZhaoDepartment of Geriatric Medicine, The First Hospital of Jilin University, Changchun 130021, People’s Republic of ChinaTel +86-431-88783239Fax +86-431-88786439Email zhaohuiyingjdyy@126.comSongyan LiuDepartment of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province 130021, People’s Republic of ChinaTel +86-431-84595348Fax +86-431-84596133Email songyanliujilin@163.comPurpose: To explore the neuroprotective effects and mechanisms of Apelin (APLN), and to study the regulation of APLN expression by microRNA (miRNA) in epilepsy.Materials and Methods: In vitro and in vivo epileptic models were established with hippocampal neurons and Wistar rats. Apoptosis of neurons was identified by flow cytometry. Western blotting was used to detect the expression of proteins, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to analyze the expression of miRNA and messenger RNA (mRNA). Bioinformatics software was used to predict target genes of miRNA, which were confirmed by dual-luciferase reporter gene system and functional experiments.Results: Our study demonstrated protective effects of APLN against neuronal death in epilepsy both in vitro and in vivo. The underlying mechanisms involved are inhibiting the expression of metabotropic glutamate receptor 1 (mGluR1), Bax, and caspase-3; promoting the expression of Bcl-2; and increasing phosphorylated-AKT (p-AKT) levels in neurons. For the first time, we found that miR-182 could negatively regulate both transcriptional and translational levels of APLN, and that the up-regulation of miR-182 inhibited the expression of APLN and Bcl-2, and promoted the expression of Bax and caspase-3.Conclusion: APLN could protect the neurons from injury in epilepsy by regulating the expression of apoptosis-associated proteins and mGluR1 and increasing p-AKT levels, which were attenuated by miR-182. Hence, miR-182/APLN may be potential targets for epilepsy control and treatment.Keywords: epilepsy, apelin, neuroprotective effects, miR-182, regulation
format article
author Dong H
Dong B
Zhang N
Liu S
Zhao H
author_facet Dong H
Dong B
Zhang N
Liu S
Zhao H
author_sort Dong H
title microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
title_short microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
title_full microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
title_fullStr microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
title_full_unstemmed microRNA-182 Negatively Influences the Neuroprotective Effect of Apelin Against Neuronal Injury in Epilepsy
title_sort microrna-182 negatively influences the neuroprotective effect of apelin against neuronal injury in epilepsy
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/819b05184c634e61bd77dd5dd3b63bfb
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AT zhangn microrna182negativelyinfluencestheneuroprotectiveeffectofapelinagainstneuronalinjuryinepilepsy
AT lius microrna182negativelyinfluencestheneuroprotectiveeffectofapelinagainstneuronalinjuryinepilepsy
AT zhaoh microrna182negativelyinfluencestheneuroprotectiveeffectofapelinagainstneuronalinjuryinepilepsy
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